Biomedical Papers-Olomouc最新文献

Background: Obesity and related metabolic diseases are becoming a worldwide epidemic, leading to increased mortality and heavy medical costs. Our Chinese herbal formula Xiao-Gao-Jiang-Zhuo (XGJZ) has remarkable effects on curing obese patients in the clinic, but the cellular and molecular basis remains unknown. This study aimed to reveal the molecular mechanism involved in adipogenesis in vitro.

Methods: Chinese herbal formula XGJZ-containing serum was prepared from XGJZ-treated obesity model rats. The function of XGJZ-containing serum was validated in 3T3-L1 preadipocytes. Oil O staining was performed to determine intracellular lipid accumulation in differentiated 3T3-L1 cells. The expression of pro-adipogenic transcription factors was measured to further validate the adipogenesis of 3T3-L1 adipocytes. The contents of triglyceride (TG), free fatty acid (FFA), and glycerin, along with the activities of lipid metabolism-related enzymes (including FAT, FATP1, DGAT, GPAT, ATGL, and HSL) were measured to study the lipogenesis in 3T3-L1 adipocytes.

Results: XGJZ-containing serum inhibited 3T3-L1 differentiation, decreased intracellular lipid accumulation, and suppressed the expression of pro-adipogenic transcription factors in differentiated 3T3-L1 cells. The contents of TG, FFA, and glycerin were decreased when treated with XGJZ-containing serum, which also modulated lipid metabolism-related enzyme activities. The activities of fatty acid transporters (FAT, FATP1) and lipid mobilization enzymes (ATGL, HSL) were promoted, while activities of triglyceride biosynthesis enzymes (DGAT, GPAT) were attenuated in differentiated 3T3-L1 cells.

Conclusion: XGJZ-containing serum has inhibitory effects on adipogenesis in 3T3-L1 preadipocytes, affirming the effect of XGJZ in treating obesity. It provides evidence for the mechanism of obesity.

Backround: The goal of assisted reproduction is for a couple treated with IVF techniques to end the treatment by giving birth to a healthy baby. A neccessary presumption for success is the identification of the best embryo with high implantation and developmental potential. One option is to select an euploid embryo by invasive preimplantaion genetic testing for aneuploidy (PGT-A) or it is possible to select the best embryo by non-invasive time-lapse monitoring (TLM), specifically based on morphokinetic parameters and morphological markers that are able to identify an embryo with high developmental potential.

Materials and methods: The study involved a total of 1060 embryos (585 euploid and 475 aneuploid embryos after PGT-A) with good morphology from 329 patients in the period 01/2016-10/2021. All embryos were cultured in a time-lapse incubator, trophectoderm (TE) cells biopsies for PGT-A examination were performed on day 5 (D5) or day 6 (D6) of culture. During the study period, 225 frozen embryo transfers (FET) of one euploid embryo were performed. Based on the treatment outcome, the embryos were divided into 2 groups - euploid embryos, which led to the birth of a healthy child, and euploid embryos that did not show fetal heartbeat (FHB) after FET.

Results: Based on the statistical analysis of the embryos without implantation and the embryos with live birth, it is clear that the morphokinetic parameters t5 (time of division into 5 cells) and tSB (time of start of blastulation) are significantly different.

Conclusion: The results suggest that of the morphokinetic parameters tSB and t5 are predictive indicators for selecting an embryo with high developmental potential and with a high probability of achieving the birth of a healthy child.

Background: We report four pediatric subjects with Cushing's disease (CD) diagnosed in the Czech Republic. We focus on initial symptoms of Cushing's syndrome (CS) which can lead to early diagnosis, on typical symptoms of CS in children, their age and sex distribution, the mean length of symptoms prior to diagnosis, indication for examination, post-cure growth, sexual development and pituitary function in our four CD patients after transsphenoidal pituitary surgery (TSS). We describe the diagnostic process leading to confirmation of CD and we emphasize the biochemical and radiological diagnostic difficulties.

Conclusions: Pediatric CD has a number of features distinct from adult CD. Our retrospective analysis confirmed the presence of growth retardation and change in facial appearance with development of moon face as the first symptoms of CS. According to our observation, growth retardation is prior to development of moon face. The other typical symptoms frequently seen in pediatric patients are pseudo-precocious puberty in both sexes, hirsutism in pubertal girls due to excessive adrenal androgen secretion and pubertal delay. A corticotropin-releasing hormone (CRH) test and especially bilateral inferior petrosal sinus sampling for ACTH (BIPSS) contribute to confirming the diagnosis of CD and excluding ectopic ACTH syndrome in children with unvisible adenoma on pituitary magnetic resonance imaging (MRI).

Atrial fibrillation (AF), the most common cardiac arrhythmia is associated with increased morbidity and mortality. The higher mortality is due to the risk of heart failure and cardioembolic events. This in-depth review focuses on the strategies and efficacy of catheter ablation for non-paroxysmal atrial fibrillation. The main medical databases were searched for contemporary studies on catheter ablation for non-paroxysmal AF. Catheter ablation is currently proven to be the most effective treatment for AF and consists of pulmonary vein isolation as the cornerstone plus additional ablations. In terms of SR maintenance, it is less effective in non-paroxysmal AF than in paroxysmal patients. but the clinical benefit in non-paroxysmal patients is substantially higher. Since pulmonary vein isolation is ineffective, a variety of techniques have been developed, e.g. linear ablations, ablation of complex atrial fractionated electrograms, etc. Another paradox consists in the technique of catheter ablation. Despite promising results in early observation studies, further randomized studies have not confirmed the initial enthusiasm. Recently, a new approach, pulsed-field ablation, appears promising. This is an in-depth summary of current technologies and techniques for the ablation of non-paroxysmal AF. We discuss the benefits, risks and implications in the treatment of patients with non-paroxysmal AF.

Aims: To investigate DNA methylation of specific gene promoters in endometrial hyperplasia compared to normal endometrial tissue.

Materials and methods: To search for epigenetic events, methylation-specific multiplex ligation-dependent probe amplification was employed to compare the methylation status of 64 tissue samples with atypical endometrial hyperplasia, 60 tissue samples with endometrial hyperplasia without atypia, and 40 control tissue samples with normal endometrium.

Results: Differences in DNA methylation among the groups were found in PTEN, CDH13, and MSH6 promoters (PTEN: atypical hyperplasia 32%, benign hyperplasia 6.8%, normal endometrium 10%; P=0.004; CDH13: atypical hyperplasia, 50%; benign hyperplasia, 43%; normal endometrium 8.1%; P=0.003; MSH6 atypical hyperplasia 84%, benign hyperplasia, 62%; normal endometrium, 52%; P=0.008.) Higher rates of CDH13 promoter methylation were identified in the groups with both forms of endometrial hyperplasia when compared to the control group (atypical hyperplasia, P=0.003, benign hyperplasia, P=0.0002). A higher rate of DNA methylation of the PTEN and MSH6 promoters was observed in samples with atypical endometrial hyperplasia than in samples with benign endometrial hyperplasia (PTEN: P=0.02; MSH6: P=0.01) and samples with normal endometrial tissue (PTEN, P=0.04; MSH6, P=0.006).

Conclusion: DNA methylation of CDH13, PTEN, and MSH6 appear to be involved in the development of endometrial hyperplasia.

Aim: To assess nutritional status and muscle mass loss in patients with chronic obstructice pulmonary disease (COPD) from the Czech National Database of COPD and to evaluate the association of nutritional parameters with COPD phenotype, lung function, COPD-related symptoms and long-term survival.

Methods: A total of 343 patients with known body composition parameters - body mass Index (BMI), fat-free mass index (FFMI) and mid-art muscle circumference (MAMC) - were included in the analysis. Descriptive statistical methods were used to assess differences between groups, and overall survival was assessed using the Kaplan-Meier method after 9 years of follow-up.

Results: Nutritional imbalances were common in patients with COPD. Underweight and muscle mass loss were associated with emphysematous and pulmonary cachexia phenotypes, worse lung function, more symptoms and exacerbations, osteoporosis and depression. Overweight and obesity were associated with a chronic bronchitis phenotype and cardiovascular and metabolic comorbidities. Obese patients had higher forced exspiratory volume in 1 second (FEV₁) and diffusing capacity of the lung for carbon monoxid (DL_CO), but lower forced exspiratory capacity (FVC). Malnutrition increased the risk of death. Cachexia and underweight reduced median survival from 72.0 to 43.5 (P=0.049) and 39.8 (P=0.010) months, respectively, compared to normal nutrition. Muscle mass loss by MAMC of ≥20% was the strongest predictor of mortality, increasing the risk of death by 5.5-fold compared to patients with normal muscle mass (P<0.001). Patients with overweight and obesity had a 40% (P=0.026) and 30% lower risk of death, respectively, compared to patients with normal nutrition.

Conclusions: Patients with COPD often have nutritional imbalances. That is an important determinant of clinical characteristics and outcomes in patients with COPD. Further research is needed to better understand these differences.

Background: Rehabilitation may be an effective additional treatment method in patients with obstructive sleep apnea (OSA). Physical exercise, weight reduction, pulmonary rehabilitation, and myofunctional therapy (MT) represent beneficial components of rehabilitation recommended as a possible adjunct to standard OSA treatment.

Methods and results: A 54-year-old man with morbid obesity, long-lasting snoring, breathing pauses, frequent waking, as well as persistent drowsiness and fatigue during the day underwent polysomnography (PSG) to investigate suspected OSA. Severe OSA was confirmed by PSG and a 12-week comprehensive, home-based telerehabilitation program (tele-RHB program) along with continuous positive airway pressure (CPAP) therapy was implemented. The tele-RHB program included regular teleconsultations, aerobic-endurance training, MT, inspiratory and expiratory muscle training, as well as recommendations on proper nutrition, a healthy lifestyle, and behavioral changes. Following the treatment, the patient's quality of life (QoL), exercise capacity, lung function, and OSA severity significantly improved. The patient achieved an overall 19.9 kg reduction in weight, of which 16.2 kg was body fat, and his apnea-hypopnea index decreased by 42.6 episodes/hour.

Conclusion: Our case report suggests that the comprehensive home-based tele-RHB program adjunct to CPAP therapy may be a novel approach for improving OSA severity, a patient's QoL, exercise capacity, lung function and body composition. It is important to note that such a program should be optional, however it may be needed to achieve the highest possible overall improvement in a patient's life. Further clinical investigations are needed to determine the therapeutic efficacy and clinical potential of this tele-RHB program.

The aim of this review is to provide a comprehensive analysis of the existing literature pertaining to cytology of extrahepatic bile ducts. A search using the keywords "biliary brush cytology" was conducted in the PubMed database, with a focus on recent articles. The inclusion criteria primarily encompassed publications addressing problematic biliary stenosis. Emphasis was placed on identifying articles that explored innovative or less-utilized examination techniques aimed at enhancing the sensitivity of cytological examination. This review presents a comprehensive overview of the various types of materials used in sampling and the corresponding sampling methods. Additionally, it explores cytological and cytogenetic techniques, such as fluorescence in situ hybridization (FISH) and genetic methods (miRNA, NGS, cfDNA). These techniques possess the potential to improve the accuracy of diagnosing bile duct tumors, although their sensitivity varies. Furthermore, their utilization can facilitate early therapy, which plays a crucial role in patient prognosis. Each examination is always dependent on the quality and quantity of material delivered. A higher sensitivity of these examinations can be achieved by combining biliary cytology and other complementary methods.

Aims: To evaluate the 3-year follow-up results of two children delivered at our institution in 2019 from mothers with a transplanted uterus.

Methods: Observational data on pregnancy outcomes, neonatal course, and growth trajectory in two children born to mothers after uterus transplantation, including 3-year follow-up and neurodevelopmental status assessed using the Bayley Scales of Infant and Toddler Development, third edition (Bayley-III).

Results: Both children were born prematurely via uneventful caesarean sections, to mothers with Mayer-Rokitansky-Küster-Hauser syndrome and a transplanted uterus. An acute caesarean section was performed in one mother because of the onset of regular uterine contractions at 34 weeks and 6 days of pregnancy; in the other mother, an elective caesarean section was performed at 36 weeks and 2 days of gestation. The children were born healthy with no congenital malformations. They had an uneventful postnatal course and showed a normal growth trajectory during 3 years of follow-up. The Bayley-III neurodevelopmental scores of both children were within the normal ranges at ages 2 and 3 years.

Conclusion: Though pregnancy after uterus transplantation is associated with the risk of premature delivery, no abnormalities were observed in the neonatal course and 3-year follow-up results, including the neurodevelopmental status, of two children born prematurely to mothers with a transplanted uterus. This is the first report on neurodevelopmental outcomes in children born after uterus transplantation. More data on children born after this radical procedure of uterine factor infertility treatment are required to support our promising results.

Background: Complex networks of chemokines are part of the immune reaction targeted against tumor cells. Chemokines influence cancer growth. It is unclear whether the concentrations of chemokines at the time of NSCLC (non-small cell lung cancer) diagnosis differ from healthy controls and reflect the extent of NSCLC.

Aims: To compare chemokine concentrations (CCL2, CCL8, CXCL12) in the plasma of patients with resectable NSCLC to those without cancer. To determine whether the chemokine concentrations differ relative to the stage of disease.

Methods: Sixty-nine patients undergoing surgery for proven/suspected NSCLC were enrolled. They underwent standard diagnostic and staging procedures to determine resectability, surgery was performed. Forty-two patients were diagnosed with NSCLC, while 27patients had benign lung lesions and functioned as the control group. Chemokine concentrations in peripheral blood were assessed using ELISA. Parametric statistics were used for the analysis of results.

Results: There were no differences in plasma chemokine concentrations in NSCLC patients compared to controls. CXCL12 concentrations correlated positively with tumor extent expressed as clinical stage, (mean values: stage I 5.08 ng/mL, SEM 0.59; stage II and IIIA 7.82 ng/mL; SEM 1.06; P=0.022). Patients with NSCLC stages II+IIIA had significantly higher CXCL12 concentrations than controls (mean values: stage II+IIIA 7.82 ng/mL; SEM 1.06; controls 5.3 ng/mL; SEM 0.46; P=0.017).

Conclusion: CXCL12 was related to tumor growth and could potentially be used as a biomarker of advanced disease.